We hypothesize that genetic variations in acute responses to alcohol influence a person's drinking habits and risk for alcohlism. Hence, we predict that an individual's initial response and acute adaptation to alcohol are both correlated with familial history for alcoholism (FHA) and recent drinking history (RDH). We also posit that manifestation of genetic influences may vary as a function of the concentration of brain's exposure to alcohol. We propose 3 projects to test our predictions. Each project employs the intravenous (iv) alcohol clamping method, shown in our recent studies to be capable of maintaining breath alcohol concentration (BrAC), and hence the brain's exposure to alcohol, at nearly constant, predeterminal levels over time.